New Zealand Black mice spontaneously develop autoimmune hemolytic anemia. Peritoneal cavity lymphocytes from NZB mice include a high proportion of cells that bind autologous erythrocytes. These cells produce anti-erythrocyte antibody that can be demonstrated when target erythrocytes are treated with bromelin. Such autoreactive cells are also present in normal mice, though in much smaller numbers. Aging and sex influence the peritoneal antierythrocyte response to bromelin-treated mouse erythrocytes. Older mice generally produce more rosettes and plaques than younger animals, and females have higher responses than males. During short-term culture in the absence of antigen, the response to bromelin-treated mouse erythrocytes increases. By contrast, the response to untreated mouse erythrocytes decreases during the same culture conditions. The in vitro response to bromelin-treated mouse erythrocytes by New Zealand Black peritoneal lymphocytes is suppressed by a cell that binds to untreated erythrocytes. The enhanced response to bromelin-treated mouse erythrocytes in culture may reflect the loss of this suppressor cell and is being presently studied.